Serum amyloid A levels are associated with polymorphic variants in the serum amyloid A 1 and 2 genes.

BACKGROUND

Serum amyloid A (SAA) is secreted by liver hepatocytes in response to increased inflammation whereupon it associates with high-density lipoprotein (HDL) and alters the protein and lipid composition of HDL negating some of its anti-atherogenic properties.

AIMS

To identify variants within the SAA gene that may be associated with SAA levels and/or cardiovascular disease (CVD).

METHODS

We identified exonic variants within the SAA genes by deoxyribonucleic acid (DNA) Sanger sequencing. We tested the association between SAA variants and serum SAA levels in 246 individuals with and without CVD.

RESULTS

Increased SAA was associated with rs2468844 (beta [β] = 1.73; confidence intervals [CI], 1.14-1.75; p = 0.01), rs1136747 (β = 1.53 (CI, 1.11-1.73); p = 0.01) and rs149926073 (β = 3.37 (CI, 1.70-4.00); p = 0.02), while rs1136745 was significantly associated with decreased SAA levels (β = 0.70 (CI, 0.53-0.94); p = 0.02). Homozygous individuals with the SAA1.3 haplotype had significantly lower levels of SAA compared with those with SAA1.1 or SAA1.5 (β = 0.43 (CI, 0.22-0.85); p = 0.02) while SAA1.3/1.5 heterozygotes had significantly higher SAA levels compared with those homozygous for SAA1.1 (β = 2.58 (CI, 1.19-5.57); p = 0.02).

CONCLUSIONS

We have identified novel genetic variants in the SAA genes associated with SAA levels, a biomarker of inflammation and chronic disease. The utility of SAA as a biomarker for inflammation and chronic disease may be influenced by underlying genetic variation in baseline levels.